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Numerical models solved on adaptive moving meshes have become increasingly prevalent in recent years. Motivating problems include the study of fluids in a Lagrangian frame and the presence of highly localized structures such as shock waves or interfaces. In the former case, Lagrangian solvers move the nodes of the mesh with the dynamical flow; in the latter, mesh resolution is increased in the proximity of the localized structure. Mesh adaptation can include remeshing, a procedure that adds or removes mesh nodes according to specific rules reflecting constraints in the numerical solver. In this case, the number of mesh nodes will change during the integration and, as a result, the dimension of the model's state vector will not be conserved. This work presents a novel approach to the formulation of ensemble data assimilation (DA) for models with this underlying computational structure. The challenge lies in the fact that remeshing entails a different state space dimension across members of the ensemble, thus impeding the usual computation of consistent ensemble-based statistics. Our methodology adds one forward and one backward mapping step before and after the ensemble Kalman filter (EnKF) analysis, respectively. This mapping takes all the ensemble members onto a fixed, uniform reference mesh where the EnKF analysis can be performed. We consider a high-resolution (HR) and a low-resolution (LR) fixed uniform reference mesh, whose resolutions are determined by the remeshing tolerances. This way the reference meshes embed the model numerical constraints and are also upper and lower uniform meshes bounding the resolutions of the individual ensemble meshes. Numerical experiments are carried out using 1-D prototypical models: Burgers and Kuramoto–Sivashinsky equations and both Eulerian and Lagrangian synthetic observations. While the HR strategy generally outperforms that of LR, their skill difference can be reduced substantially by an optimal tuning of the data assimilation parameters. The LR case is appealing in high dimensions because of its lower computational burden. Lagrangian observations are shown to be very effective in that fewer of them are able to keep the analysis error at a level comparable to the more numerous observers for the Eulerian case. This study is motivated by the development of suitable EnKF strategies for 2-D models of the sea ice that are numerically solved on a Lagrangian mesh with remeshing.

Abstract Meniscus-derived stem cells (MeSCs), a unique type of MSC, have outstanding advantages in meniscal cytotherapy and tissue engineering, but the effects and molecular mechanisms of PBM on MeSCs are still unclear. We used 660-nm LED light with different energy densities to irradiate six human MeSC samples and tested their proliferation rate via cell counting, chondrogenic differentiation capacity via the DMMB assay, mitochondrial activity via the MTT assay, and gene expression via qPCR. The proliferation ability, chondrogenic capacity and mitochondrial activity of the 18 J/cm2 group were greater than those of the 4 J/cm2 and control groups. The mRNA expression levels of Akt, PI3K, TGF-β3, Ki67 and Notch-1 in the 18 J/cm2 group were greater than those in the other groups in most samples. After chondrogenic induction, the expression of Col2A1, Sox9 and Aggrecan in the 18 J/cm2 group was significantly greater than that in the 4 J/cm2 and control groups in most of the samples. The variation in the MTT values and Src, PI3K, Akt, mTOR and GSK3β levels decreased with time. The results showed that 660-nm LED red light promoted proliferation and chondrogenic differentiation and affected the gene expression of MeSCs, and the effects on gene expression and mitochondrial activity decreased with time.

Abstract The megadiverse plant family Asteraceae forms an iconic component of island floras including many spectacular radiations, but a global picture of its insular diversity is lacking. Here, we uncover the global biogeographical and evolutionary patterns of Asteraceae on islands to reveal the magnitude and potential causes of their evolutionary success. We compile a global checklist of Asteraceae species native and endemic to islands and combine it with macroecological analyses and a phylogenetic review of island radiations. Asteraceae have a global distribution on islands, comprising approximately 6,000 native island species, with 58% endemics. While diversity of the family on islands is lower than expected given its overall diversity, Asteraceae are the most diverse family on oceanic islands, suggesting an exceptional ability to thrive in isolation. In agreement with island biogeography predictions, native Asteraceae diversity increases with area and decreases with isolation, while endemism increases with both. We identify 39 confirmed island radiations and 69 putative radiations, exceeding numbers for other iconic insular groups. Our results reveal Asteraceae offer immense potential for research in ecology and evolution, given their close tracking of island biogeography expectations, large number of both species and radiations, cosmopolitan distribution, and numerous undiscovered radiations.

Abstract There is currently limited data on the effectiveness of COVID-19 vaccines for children aged 6–11 years in Malaysia. This study aims to determine vaccine effectiveness (VE) against COVID-19-related hospitalization after receipt of one- and two-doses of BNT162b2 mRNA (Comirnaty-Pfizer/BioNTech) vaccine over a duration of almost 1 year in the predominantly Omicron period of BA.4/BA.5 and X.B.B sub lineages. This study linked administrative databases between May 2022 and March 2023 to evaluate real-world vaccine effectiveness (VE) for the BNT162b2 mRNA (Comirnaty-Pfizer/BioNTech) vaccine against COVID-19-related hospitalization in the Omicron pre-dominant period with BA.4/BA.5 and X.B.B sub lineages. During the Omicron-predominant period, the cumulative hospitalization rate was almost two times higher for unvaccinated children (9.6 per million population) compared to vaccinated children (6 per million population). The estimated VE against COVID-19 hospitalization for one dose of BNT162b2 was 27% (95% CI − 1%, 47%) and 38% (95% CI 27%, 48%) for two doses. The estimated VE against hospitalization remained stable when stratified by time. VE for the first 90 days was estimated to be 45% (95% CI 33, 55%), followed by 47% (95% CI 34, 56%) between 90 and 180 days, and 36% (95% CI 22, 45%) between 180 and 360 days. Recent infection within 6 months does not appear to modify the impact of vaccination on the risk of hospitalization, subject to the caveat of potential underestimation. In our pediatric population, BNT162b2 provided moderate-non-diminishing protection against COVID-19 hospitalization over almost 1 year of Omicron predominance.

Abstract Genomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.

Abstract Excess mortalities are a more accurate indicator of true COVID-19 disease burden. This study aims to investigate levels of excess all-cause mortality and their geographic, age and sex distributions between January 2020-September 2021. National mortality data between January 2016 and September 2021 from the Department of Statistics Malaysia was utilised. Baseline mortality was estimated using the Farrington algorithm and data between 1 January 2016 and 31 December 2019. The occurrence of excess all-cause mortality by geographic-, age- and sex-stratum was examined from 1 January 2020 to 30 September 2021. A sub-analysis was also conducted for road-traffic accidents, ethnicity and nationality. Malaysia had a 5.5–23.7% reduction in all-cause mortality across 2020. A reversal is observed in 2021, with an excess of 13.0–24.0%. Excess mortality density is highest between July and September 2021. All states and sexes reported excess trends consistent with the national trends. There were reductions in all all-cause mortalities in individuals under the age of 15 (0.4–8.1%) and road traffic accident-related mortalities (36.6–80.5%). These reductions were higher during the first Movement Control Order in 2020. Overall, there appears to be a reduction in all-cause mortality for Malaysia in 2020. This trend is reversed in 2021, with excess mortalities being observed. Surveillance of excess mortalities can allow expedient detection of aberrant events allowing timely health system and public health responses.

This study develops a novel approach to forecasting anomalies of meat yield from mussel aquaculture in Pelorus Sound, New Zealand, based on the relationships between non-local sea surface temperature (SST) and observations of mussel meat yield over 13 years. Overall, we found strong associations between lagged SSTs in the Tasman Sea region and mussel meat yield, with a noticeable seasonal cycle in these relationships. Results also showed that oceanic variables such as SST correlate more strongly with mussel meat yield than atmospheric variables, such as surface wind and other indices of atmospheric flow. The relationship between SST and mussel meat yield is linked to patterns of surface wind anomalies along the west coast of New Zealand. We identified regions where the SST was most correlated with mussel meat yield anomalies for each season and derived empirical relationships from linear regression. We then applied these empirical relationships to seasonal forecasts of SST from the European Centre for Medium-Range Weather Forecasts to generate seasonal forecasts of mussel meat yield. By validating our mussel meat yield forecasts from 13 years of retrospective forecasts, we find significant skill at lead times of up to 3 months in December–February and 5 months in September–November. During March-August forecasts are only skillful at a lead-time of 1 month. The results of this study have the potential to improve the accuracy and reliability of mussel meat yield forecasts and to provide valuable insights for the mussel industry.

Abstract Hemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011–2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P

IntroductionAs the rate of end-stage kidney disease rises, there is an urgent need to consider the catastrophic health expenditure of post-transplantation care. Even a small amount of out-of-pocket payment for healthcare can negatively affect households' financial security. This study aims to determine the association between socioeconomic status and the prevalence of catastrophic health expenditure in post-transplantation care.MethodA multi-centre cross-sectional survey was conducted in person among 409 kidney transplant recipients in six public hospitals in the Klang Valley, Malaysia. Catastrophic health expenditure is considered at 10% out-of-pocket payment from household income used for healthcare expenditure. The association of socioeconomic status with catastrophic health expenditure is determined via multiple logistic regression analysis.Results93 kidney transplant recipients (23.6%) incurred catastrophic health expenditures. Kidney transplant recipients in the Middle 40% (RM 4360 to RM 9619 or USD 1085.39 -USD 2394.57) and Bottom 40% (RM 9619 or > USD 2394.57) income group. Kidney transplant recipients in the Bottom 40% and Middle 40% income groups were more susceptible to catastrophic health expenditure at 2.8 times and 3.1 times compared to higher-income groups, even under the care of the Ministry of Health.ConclusionUniversal health coverage in Malaysia cannot address the burden of out-of-pocket healthcare expenditure on low-income Kidney transplant recipients for long-term post-transplantation care. Policymakers must reexamine the healthcare system to protect vulnerable households from catastrophic health expenditures.

Background and aims: Kidney injury is associated with serious short and long-term morbidities, increased risk of death and stupendous healthcare costs. The objective of this study was to investigate the therapeutic role of Kidney Revival (KR), an herbal formulation, on gentamicin-induced kidney injury in animals.Methods: The antioxidant properties of KR were studied using the DPPH assay and hydrogen peroxide, nitric oxide and superoxide radical scavenging. Moreover, the therapeutic application of KR was studied in acute oral toxicity in mice and gentamicin-induced renal toxicity in rats. All clinical, pathological and biochemical features related to kidney injury were carefully studied.Results: In vitro experiments showed free radical scavenging properties of KR. Acute oral toxicity investigations revealed that KR was safe up to 2 ml/kg. Treatment with KR in gentamicin-induced nephrotoxic animals showed a significant (p

[This corrects the article DOI: 10.1371/journal.pone.0008925.].

[This corrects the article DOI: 10.1371/journal.pone.0249394.].

A rip current is a strong, localized current of water which moves along and away from the shore. Recent studies have suggested that drownings due to rip currents are still a major threat to beach safety. Identification of rip currents is important for lifeguards when making decisions on where to designate patrolled areas. The public also require information while deciding where to swim when lifeguards are not on patrol. In the present study we present an artificial intelligence (AI) algorithm that both identifies whether a rip current exists in images/video, and also localizes where that rip current occurs. While there have been some significant advances in AI for rip current detection and localization, there is a lack of research ensuring that an AI algorithm can generalize well to a diverse range of coastal environments and marine conditions. The present study made use of an interpretable AI method, gradient-weighted class-activation maps (Grad-CAM), which is a novel approach for amorphous rip current detection. The training data/images were diverse and encompass rip currents in a wide variety of environmental settings, ensuring model generalization. An open-access aerial catalogue of rip currents were used for model training. Here, the aerial imagery was also augmented by applying a wide variety of randomized image transformations (e.g., perspective, rotational transforms, and additive noise), which dramatically improves model performance through generalization. To account for diverse environmental settings, a synthetically generated training set, containing fog, shadows, and rain, was also added to the rip current images, thus increased the training dataset approximately 10-fold. Interpretable AI has dramatically improved the accuracy of unbounded rip current detection, which can correctly classify and localize rip currents about 89% of the time when validated on independent videos from surf-cameras at oblique angles. The novelty also lies in the ability to capture some shape characteristics of the amorphous rip current structure without the need of a predefined bounding box, therefore enabling the use of remote technology like drones. A comparison with well-established coastal image processing techniques is also presented via a short discussion and easy reference table. The strengths and weaknesses of both methods are highlighted and discussed.

Background Cardiovascular diseases (CVDs) are the number cause of death worldwide. In Ghana CVD has been the leading cause of death since 2001. The prevalence of CVD risk factors among adolescents in Ghana has been increasing. This study seeks to develop, implement and evaluate the effects of a behavioral modification intervention program to reduce CVD risk factors among secondary school students in Brong Ahafo, Ghana. Methods A cluster-randomized controlled trial was conducted with schools as clusters over a period of six-months with pre and post intervention evaluations. Participants were public secondary school students (14–19 years) from four schools in Brong Ahafo, Ghana. Students in the intervention group were trained by the researchers whereas those of the control group received no intervention. The intervention included health education and physical activity modules. Follow-up data using same questionnaire were collected within two weeks after the intervention was completed. Intention-to-treat analysis was performed after replacing missing values using the multiple imputation method. The generalized linear mixed model (GLMM) was used to assess the effects of the intervention study. Results The GLMM analyses showed the intervention was effective in attaining 0.77(pConclusion There is an urgent need for the intervention program to be integrated into the existing curriculum structure of secondary school schools. Implementing the intervention will allow for longer and more consistent impact on the reduction of CVD risk factors among secondary school students.

IntroductionThe reporting of Coronavirus Disease 19 (COVID-19) mortality among healthcare workers highlights their vulnerability in managing the COVID-19 pandemic. Some low- and middle-income countries have highlighted the challenges with COVID-19 testing, such as inadequate capacity, untrained laboratory personnel, and inadequate funding. This article describes the components and implementation of a healthcare worker surveillance programme in a designated COVID-19 teaching hospital in Malaysia. In addition, the distribution and characteristics of healthcare workers placed under surveillance are described.Material and methodsA COVID-19 healthcare worker surveillance programme was implemented in University Malaya Medical Centre. The programme involved four teams: contact tracing, risk assessment, surveillance and outbreak investigation. Daily symptom surveillance was conducted over fourteen days for healthcare workers who were assessed to have low-, moderate- and high-risk of contracting COVID-19. A cross-sectional analysis was conducted for data collected over 24 weeks, from the 6th of March 2020 to the 20th of August 2020.ResultsA total of 1,174 healthcare workers were placed under surveillance. The majority were females (71.6%), aged between 25 and 34 years old (64.7%), were nursing staff (46.9%) and had no comorbidities (88.8%). A total of 70.9% were categorised as low-risk, 25.7% were moderate-risk, and 3.4% were at high risk of contracting COVID-19. One-third (35.2%) were symptomatic, with the sore throat (23.6%), cough (19.8%) and fever (5.0%) being the most commonly reported symptoms. A total of 17 healthcare workers tested positive for COVID-19, with a prevalence of 0.3% among all the healthcare workers. Risk category and presence of symptoms were associated with a positive COVID-19 test (pConclusionCOVID-19 symptom surveillance and risk-based assessment have merits to be included in a healthcare worker surveillance programme to safeguard the health of the workforce.

On March 24, 2020 India implemented a national lockdown to prevent spread of the novel Coronavirus disease (COVID-19) among its 1.3 billion people. As the pandemic may disproportionately impact women and girls, this study examines gender differences in knowledge of COVID-19 symptoms and preventive behaviors, as well as the adverse effects of the lockdown among adolescents and young adults. A mobile phone-based survey was implemented from April 3-22, 2020 in Uttar Pradesh and Bihar among respondents randomly selected from an existing cohort study. Respondents answered questions related to demographics, COVID-19 knowledge, attitudes, and preventive behaviors practiced, and impacts on social, economic and health outcomes. Descriptive analyses and linear probability regression models were performed for all participants and separately for men and women. A total of 1,666 adolescents and young adults (18-24 years old) were surveyed; 70% were women. While most participants had high awareness of disease symptoms and preventive behaviors, there was variation by gender. Compared to men, women were seven percentage points (pp) less likely to know the main symptoms of COVID-19 (coeff = -0.071; 95% confidence interval: -0.122 - -0.021). Among women, there was variation in knowledge by education level, urban residence, and household wealth. Women were 22 pp less likely to practice key preventive behaviors compared to men (coeff = -0.222; 95% CIL -0.263, -0.181). Women were also more likely to report recent depressive symptoms than men (coeff = 0.057; 95% CI: 0.004, 0.109). Our findings underscore that COVID-19 is already disproportionately impacting adolescent girls and young women and that they may require additional targeted, gender-sensitive messaging to foster behavior change. Gender-sensitive information campaigns and provision of health services must be accessible and provide women and girls with needed resources and support during the pandemic to ensure gains in public health and gender equity are not lost.

Abstract The role of hepatitis virus infection in glucose homeostasis is uncertain. We examined the associations between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the development of diabetes in a cohort (N = 439,708) of asymptomatic participants in health screening examinations. In cross-sectional analyses, the multivariable-adjusted odds ratio for prevalent diabetes comparing hepatitis B surface antigen (HBsAg) (+) to HBsAg (−) participants was 1.17 (95% CI 1.06–1.31; P = 0.003). The corresponding odds ratio comparing hepatitis C antibodies (HCV Ab) (+) to HCV Ab (−) participants was 1.43 (95% CI 1.01–2.02, P = 0.043). In prospective analyses, the multivariable-adjusted hazard ratio for incident diabetes comparing HBsAg (+) to HbsAg (−) participants was 1.23 (95% CI 1.08–1.41; P = 0.007). The number of incident cases of diabetes among HCV Ab (+) participants (10 cases) was too small to reliably estimate the prospective association between HCV infection and diabetes. In this large population at low risk of diabetes, HBV and HCV infections were associated with diabetes prevalence and HBV infection with the risk of incident diabetes. Our studies add evidence suggesting that diabetes is an additional metabolic complication of HBV and HCV infection.

The Sea surface KInematics Multiscale monitoring (SKIM) satellite mission is designed to explore ocean surface current and waves. This includes tropical currents, notably the poorly known patterns of divergence and their impact on the ocean heat budget, and monitoring of the emerging Arctic up to 82.5°N. SKIM will also make unprecedented direct measurements of strong currents, from boundary currents to the Antarctic circumpolar current, and their interaction with ocean waves with expected impacts on air-sea fluxes and extreme waves. For the first time, SKIM will directly measure the ocean surface current vector from space. The main instrument on SKIM is a Ka-band conically scanning, multi-beam Doppler radar altimeter/wave scatterometer that includes a state-of-the-art nadir beam comparable to the Poseidon-4 instrument on Sentinel 6. The well proven Doppler pulse-pair technique will give a surface drift velocity representative of the top meter of the ocean, after subtracting a large wave-induced contribution. Horizontal velocity components will be obtained with an accuracy better than 7 cm/s for horizontal wavelengths larger than 80 km and time resolutions larger than 15 days, with a mean revisit time of 4 days for of 99% of the global oceans. This will provide unique and innovative measurements that will further our understanding of the transports in the upper ocean layer, permanently distributing heat, carbon, plankton, and plastics. SKIM will also benefit from co-located measurements of water vapor, rain rate, sea ice concentration, and wind vectors provided by the European operational satellite MetOp-SG(B), allowing many joint analyses. SKIM is one of the two candidate satellite missions under development for ESA Earth Explorer 9. The other candidate is the Far infrared Radiation Understanding and Monitoring (FORUM). The final selection will be announced by September 2019, for a launch in the coming decade.

Increasing incidences of dengue have become a global health threat with major clinical manifestation including high fever and gastrointestinal symptoms. These symptoms were also expressed among Blastocystis sp. infected individuals, a parasite commonly seen in human stools. This parasite has been previously reported to replicate faster upon exposure to high temperature. The present study is a hospitalized-based cross-sectional study involved the collection of faecal sample from dengue patients. Stool examination was done by in vitro cultivation to isolate Blastocystis sp. Growth pattern of all the positive isolates were analyzed to identify the multiplication rate of Blastocystis sp. isolated from dengue patients. Distribution of Blastocystis sp. among dengue patients was 23.6%. Dengue patients who were positive for Blastocystis sp. infection denoted a significantly higher fever rate reaching 38.73°C (p

IntroductionEnd-stage renal disease (ESRD) is increasing globally, and renal transplantation (RT) is the preferred renal replacement therapy to treat ESRD. Internationally, there are only a few countries with RT rates above 50 per million population (pmp), while most of the countries have RT rates between 30-40 pmp. The low- and middle-income countries (LMIC) makes up the majority for the RT rates below 20 pmp in which Malaysia belongs to despite its increasing ESRD rates. There is a need to explore the barriers to access RT with targeted solutions to improve the RT rates and service in LMIC. Thus, a qualitative study was undertaken in Malaysia to address this issue.MethodA qualitative methodological approach was performed between March-May 2018. Semi-structured interviews were used to explore current RT policy and service availability. Key-informants were identified from a detailed stakeholder analysis of RT system in Malaysia. Interviews were digitally audio-recorded, transcribed verbatim, coded with ATLAS.ti software and underwent thematic analysis thoroughly.ResultsEight key-informants participated in the study. Barriers and related solutions were classified using the socio-ecological model (SEM). As reported, the barriers and solutions of RT in Malaysia are the results of a complex interplay of personal, cultural, and environmental factors. Key barriers are linked to public's attitude and perception towards RT and the unaccommodating practices in the healthcare fraternity for RT. Key-informants provided a systematic solution that shed light on how RT could be improved at each SEM level via effective communication, education and inter-agency collaboration.ConclusionThe SEM provided a framework to foster a better understanding of current practice, barriers, and solutions to RT in Malaysia. This study is the first to explore the barriers and related solutions to RT comprehensively as a whole. Implications of these findings could prompt a policy change for a better RT service delivery model not just for Malaysia but also for other LMIC. Further stakeholder engagement and evaluation of the systems are required to provide insight into best practices that will help to improve the RT rates and service in Malaysia.

Distinguishing between Crohn's Disease (CD) and Intestinal Tuberculosis (ITB) has been a challenging task for clinicians due to their similar presentation. CD4+FOXP3+ T regulatory cells (Tregs) have been reported to be increased in patients with pulmonary tuberculosis. However, there is no such data available in ITB. The aim of this study was to investigate the differential expression of FOXP3+ T cells in patients with ITB and CD and its utility as a biomarker.The study prospectively recruited 124 patients with CD, ITB and controls: ulcerative colitis (UC) and patients with only haemorrhoidal bleed. Frequency of CD4+CD25+FOXP3+ Tregs in peripheral blood (flow cytometry), FOXP3 mRNA expression in blood and colonic mucosa (qPCR) and FOXP3+ T cells in colonic mucosa (immunohistochemistry) were compared between controls, CD and ITB patients.Frequency of CD4+CD25+FOXP3+ Treg cells in peripheral blood was significantly increased in ITB as compared to CD. Similarly, significant increase in FOXP3+ T cells and FOXP3 mRNA expression was observed in colonic mucosa of ITB as compared to CD. ROC curve showed that a value of >32.5% for FOXP3+ cells in peripheral blood could differentiate between CD and ITB with a sensitivity of 75% and a specificity of 90.6%.Phenotypic enumeration of peripheral CD4+CD25+FOXP3+ Treg cells can be used as a non-invasive biomarker in clinics with a high diagnostic accuracy to differentiate between ITB and CD in regions where TB is endemic.

The risk of development of active TB in HIV-infected individuals is 20-37 times higher than those that are HIV negative. Poor knowledge of TB amongst people living with HIV has been associated with high transmission.To determine the effectiveness of a new health education intervention module in improving knowledge, attitude, and practice (KAP) regarding tuberculosis among HIV patients in General Hospital Minna, Nigeria.A randomized control trial was carried out from July 2015 to June 2017. A random number generating program was used to allocate 226 respondents into 2 groups. The intervention group received health education regarding tuberculosis using the developed module. The control group received the normal services provided for HIV patients. Data were collected from December 2015 to September 2016 at baseline, immediate post intervention, three, six and nine months. The outcome measures were knowledge, attitude, and practice.There was no significant difference with respect to socio-demographic characteristics, KAP of the respondents in the intervention and control group at baseline. However, there was significant improvement in knowledge in the intervention group compared to the control group, group main effect (F = (1,218) = 665.889, p = 0.001, partial ἠ2 = 0.753, d = 5.4); time (F = (3.605, 218) = 52.046, p = 0.001, partial ἠ2 = 0.193, d = 1.52) and interaction between group with time (F = (3.605, 218) = 34.028, p = 0.001, partial ἠ2 = 0.135, d = 1.23). Likewise, there was significant improvement in attitude, group main effect (p = 0.001, d = 1.26) and time (p = 0.001, p, d = 0.65). Similarly, there was improvement in practice, group main effect, time, and interaction of group with time (p < 0.05).The health education intervention program was effective in improving KAP regarding tuberculosis among HIV patients.

Adherence to treatment remains the cornerstone of long term viral suppression and successful treatment outcomes among patients receiving Antiretroviral Therapy (ART).Evaluate the effectiveness of mobile phone reminders and peer counseling in improving adherence and treatment outcomes among HIV positive patients on ART in Malaysia.A single-blind, parallel group RCT conducted in Hospital Sungai Buloh, Malaysia in which 242 adult Malaysian patients were randomized to intervention or control groups. Intervention consisted of a reminder module delivered through SMS and telephone call reminders by trained research assistants for 24 consecutive weeks (starting from date of ART initiation), in addition to adherence counseling at every clinic visit. The length of intended follow up for each patient was 6 months. Data on adherence behavior of patients was collected using specialized, pre-validated Adult AIDS Clinical Trial Group (AACTG) adherence questionnaires. Data on weight, clinical symptoms, CD4 count and viral load tests were also collected. Data was analyzed using SPSS version 22 and R software. Repeated measures ANOVA, Friedman's ANOVA and Multivariate regression models were used to evaluate efficacy of the intervention.The response rate after 6 months follow up was 93%. There were no significant differences at baseline in gender, employment status, income distribution and residential location of respondents between the intervention and control group. After 6 months follow up, the mean adherence was significantly higher in the intervention group (95.7; 95% CI: 94.39-96.97) as compared to the control group (87.5; 95% CI: 86.14-88.81). The proportion of respondents who had Good (>95%) adherence was significantly higher in the intervention group (92.2%) compared to the control group (54.6%). A significantly lower frequency in missed appointments (14.0% vs 35.5%) (p = 0.001), lower viral load (p = 0.001), higher rise in CD4 count (p = 0.017), lower incidence of tuberculosis (p = 0.001) and OIs (p = 0.001) at 6 months follow up, was observed among patients in the intervention group.Mobile phone reminders (SMS and telephone call reminders) and peer counseling are effective in improving adherence and treatment outcomes among HIV positive patients on ART in Malaysia. These findings may be of potential benefit for collaborative adherence planning between patients and health care providers at ART commencement.

The first year of university is a particularly stressful period and can impact academic performance and students' health. The aim of this study was to evaluate the health and lifestyle of undergraduates and assess risk factors associated with psychiatric symptoms.Between September 2012 and June 2013, we included all undergraduate students who underwent compulsory a medical visit at the university medical service in Nice (France) during which they were screened for potential diseases during a diagnostic interview. Data were collected prospectively in the CALCIUM database (Consultations Assistés par Logiciel pour les Centres Inter-Universitaire de Médecine) and included information about the students' lifestyle (living conditions, dietary behavior, physical activity, use of recreational drugs). The prevalence of psychiatric symptoms related to depression, anxiety and panic attacks was assessed and risk factors for these symptoms were analyzed using logistic regression.A total of 4,184 undergraduates were included. Prevalence for depression, anxiety and panic attacks were 12.6%, 7.6% and 1.0%, respectively. During the 30 days preceding the evaluation, 0.6% of the students regularly drank alcohol, 6.3% were frequent-to-heavy tobacco smokers, and 10.0% smoked marijuana. Dealing with financial difficulties and having learning disabilities were associated with psychiatric symptoms. Students who were dissatisfied with their living conditions and those with poor dietary behavior were at risk of depression. Being a woman and living alone were associated with anxiety. Students who screened positively for any psychiatric disorder assessed were at a higher risk of having another psychiatric disorder concomitantly.The prevalence of psychiatric disorders in undergraduate students is low but the rate of students at risk of developing chronic disease is far from being negligible. Understanding predictors for these symptoms may improve students' health by implementing targeted prevention campaigns. Further research in other French universities is necessary to confirm our results.

Association of Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn's disease (CD) has been controversial due to contradictory reports. Therefore, we determined the prevalence of MAP in patients with CD and intestinal tuberculosis (ITB) and its association with clinical course.Blood and intestinal biopsies were taken from 69 CD, 32 ITB patients and 41 patients with haemorrhoidal bleed who served as controls. qPCR targeting of MAP-specific IS900 gene was used to detect the presence of MAP DNA. qPCR results were further validated by sequencing. Immunohistochemistry (IHC) was used to detect the presence of MAP antigen in biopsy specimens. CD and ITB patients were followed-up for disease course and response to therapy.The frequency of MAP-specific DNA in biopsies by qPCR was significantly higher in CD patients (23.2%, p = 0.03) as compared to controls (7.3%). No significant difference in intestinal MAP presence was observed between ITB patients (12.5%, p = 0.6) and controls (7.3%). MAP presence in blood of CD patients was 10.1% as compared to 4.9% in controls while no patients with ITB were found to be positive (p = 0.1). Using IHC for detection of MAP antigen, the prevalence of MAP in CD was 2.9%, 12.5% in ITB patients and 2.4% in controls. However, long-term follow-up of the patients revealed no significant associations between clinical characteristics and treatment outcomes with MAP positivity.We report significantly high prevalence of MAP in intestinal biopsies of CD patients. However, the presence of MAP does not affect the disease course and treatment outcomes in either CD or ITB patients.

IMPORTANCE:Intraocular pressure (IOP) reduction or stabilization is the only proven method for glaucoma management. Identifying risk factors for IOP is crucial to understand the pathophysiology of glaucoma. OBJECTIVE:To examine the associations of change in body mass index (BMI), waist circumference, and percent fat mass with change in intraocular pressure (IOP) in a large sample of Korean adults. DESIGN, SETTING AND PARTICIPANTS:Cohort study of 274,064 young and middle age Korean adults with normal fundoscopic findings who attended annual or biennial health exams from January 1, 2002 to Feb 28, 2010 (577,981 screening visits). EXPOSURES:BMI, waist circumference, and percent fat mass. MAIN OUTCOME MEASURE(S):At each visit, IOP was measured in both eyes with automated noncontact tonometers. RESULTS:In multivariable-adjusted models, the average increase in IOP (95% confidence intervals) over time per interquartile increase in BMI (1.26 kg/m2), waist circumference (6.20 cm), and percent fat mass (3.40%) were 0.18 mmHg (0.17 to 0.19), 0.27 mmHg (0.26 to 0.29), and 0.10 mmHg (0.09 to 0.11), respectively (all P < 0.001). The association was stronger in men compared to women (P < 0.001) and it was only slightly attenuated after including diabetes and hypertension as potential mediators in the model. CONCLUSIONS AND RELEVANCE:Increases in adiposity were significantly associated with an increase in IOP in a large cohort of Korean adults attending health screening visits, an association that was stronger for central obesity. Further research is needed to understand better the underlying mechanisms of this association, and to establish the role of weight gain in increasing IOP and the risk of glaucoma and its complications.

Sea ice drift strongly influences sea ice thickness distribution and indirectly controls air-sea ice-ocean interactions. Estimating sea ice drift over a large range of spatial and temporal scales is therefore needed to characterize the properties of sea ice dynamics and to better understand the ongoing changes of the climate in the polar regions. An efficient algorithm is developed for processing SAR data based on the combination of feature tracking (FT) and pattern matching (PM) techniques. The main advantage of the combination is that the FT rapidly provides the first guess estimate of ice drift in a few unevenly distributed keypoints, and PM accurately provides drift vectors on a regular or irregular grid. Thorough sensitivity analysis of the algorithm is performed, and optimal sets of parameters are suggested for retrieval of sea ice drift on various spatial and temporal scales. The algorithm has rather high accuracy (error is below 300 m) and high speed (the time for one image pair is 1 min), which opens new opportunities for studying sea ice kinematic processes. The ice drift can now be efficiently observed in the Lagrangian coordinate system on an irregular grid and, therefore, used for pointwise evaluation of the models running on unstructured meshes or for assimilation into Lagrangian models.

Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT) and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts (stomach, small intestine, cecum and colon) at various time periods post-infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b-B also modifies the host's immune responses by (1) increasing IFN-γ gene expression and decreasing IL-10 gene expression in the small intestine, and (2) elevating both IFN-γ, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis.

Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in 'second hit' hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH.

INTRODUCTION: Depression is one of the most common mental health disorders and is an emerging public health problem. The objectives of this paper were to determine the prevalence of depression, its associated factors and the predictors of depression among adults in the community of Selangor. METHODS: A cross sectional study was conducted in three districts in Selangor, from 11th June to 30th December 2012. The sampling frame was obtained from the Department of Statistics Malaysia (DOS) in May 2012, using the National Population and Housing Census 2010. Adults aged 18 years and above, living in the selected living quarters were approached to participate in the study and requested to complete a set of questionnaires. RESULTS: A total of 1,556 out of 2,152 participants participated in this study, giving an overall study response rate of 61.90%. Patient Health Questionnaire 9 (PHQ-9) was used to determine the presence of depression. The prevalence of depression was 10.3%, based on the PHQ-9 cut off point of 10 and above. Based on multiple logistic regression analysis, the predictors of depression were presence of anxiety, serious problems at work, unhappy relationship with children, high perceived stress, domestic violence, unhappy relationship with spouse, low self-esteem, unhappy relationship with family, serious financial constraint and presence of chronic diseases. When reanalyzed after removing anxiety, high perceived stress and low self-esteem, additional predictors of depression were found to be serious marital problems and religiosity. CONCLUSION: The prevalence of depression in this study is similar to that found in other studies. Findings from this study are being used as baseline data to develop an effective program to assist in the management of common mental health disorders in the community, in particular depression. The identification of predictors of depression in the community is important to identify the target population for the program.

INTRODUCTION: The prevalence of metabolic syndrome is increasing disproportionately among the different ethnicities in Asia compared to the rest of the world. This study aims to determine the differences in the prevalence of metabolic syndrome across ethnicities in Malaysia, a multi-ethnic country. METHODS: In 2004, we conducted a national cross-sectional population-based study using a stratified two-stage cluster sampling design (N = 17,211). Metabolic syndrome was defined according to the International Diabetes Federation/National Heart, Lung and Blood Institute/American Heart Association (IDF/NHLBI/AHA-2009) criteria. Multivariate models were used to study the independent association between ethnicity and the prevalence of the metabolic syndrome. RESULTS: The overall mean age was 36.9 years, and 50.0% participants were female. The ethnic distribution was 57.0% Malay, 28.5% Chinese, 8.9% Indian and 5.0% Indigenous Sarawakians. The overall prevalence of the metabolic syndrome was 27.5%, with a prevalence of central obesity, raised triglycerides, low high density lipoprotein cholesterol, raised blood pressure and raised fasting glucose of 36.9%, 29.3%, 37.2%, 38.0% and 29.1%, respectively. Among those

Climatic niche models based on native-range climatic data accurately predict invasive-range distributions in the majority of species. However, these models often do not account for ecological and evolutionary processes, which limit the ability to predict future range expansion. This might be particularly problematic in the case of invaders that occupy environments that would be considered marginal relative to the climatic niche in the native range of the species. Here, we assess the potential for future range expansion in the shrub Chromolaena odorata that is currently invading mesic savannas (>650 mm MAP) in South Africa that are colder and drier than most habitats in its native range. In a greenhouse experiment we tested whether its current distribution in South Africa can be explained by increased competitive ability and/or differentiation in drought tolerance relative to the native population. We compared aboveground biomass, biomass allocation, water use efficiency and relative yields of native and invasive C. odorata and the resident grass Panicum maximum in wet and dry conditions. Surprisingly, we found little differentiation between ranges. Invasive C. odorata showed no increased competitive ability or superior drought tolerance compared to native C. odorata. Moreover we found that P. maximum was a better competitor than either native or invasive C. odorata. These results imply that C. odorata is unlikely to expand its future range towards more extreme, drier, habitats beyond the limits of its current climatic niche and that the species' invasiveness most likely depends on superior light interception when temporarily released from competition by disturbance. Our study highlights the fact that species can successfully invade habitats that are at the extreme end of their ranges and thereby contributes towards a better understanding of range expansion during species invasions.

This study was the first to explore factors associated with emotional burnout (EB) among medical residents in Malaysia. A cross-sectional study was conducted in a universal sample of 205 medical residents in a Malaysian general hospital. The self-administered questionnaire used consisted of questions on sociodemographics and work characteristics, sources of job stress, professional fulfillment, engagement, and EB. EB was measured using the emotional exhaustion subscale, the Maslach Burnout Inventory (MBI). Mean (±SD) age of the respondents was 26.5 (±1.6). The most common source of job stress was “fear of making mistakes.” Most of the participants were dissatisfied with the increase of residentship period from one year to two years. A high level of EB was reported by 36.6% of the respondents. In multivariate analysis, the most important correlates of EB were sources of job stress, professional fulfillment, and engagement. A high prevalence of EB was found among medical residents. Sociodemographic characteristics, performance pressure, and satisfaction with policies were significantly associated with EB. Although this study was limited by its cross-sectional design, its findings posit a sufficient foundation to relevant authorities to construct, amend, and amalgamate existing and future policies.

Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.

Thecosomata is a marine zooplankton group, which played an important role in the carbonate cycle in oceans due to their shell composition. So far, there is important discrepancy between the previous morphological-based taxonomies, and subsequently the evolutionary history of Thecosomata. In this study, the remarkable planktonic sampling of TARA Oceans expedition associated with a set of various other missions allowed us to assess the phylogenetic relationships of Thecosomata using morphological and molecular data (28 S and COI genes). The two gene trees showed incongruities (e.g. Hyalocylis, Cavolinia), and high congruence between morphological and 28S trees (e.g. monophyly of Euthecosomata). The monophyly of straight shell species led us to reviving the Orthoconcha, and the split of Limacinidae led us to the revival of Embolus inflata replacing Limacina inflata. The results also jeopardized the Euthecosomata families that are based on plesiomorphic character state as in the case for Creseidae which was not a monophyletic group. Divergence times were also estimated, and suggested that the evolutionary history of Thecosomata was characterized by four major diversifying events. By bringing the knowledge of palaeontology, we propose a new evolutionary scenario for which macro-evolution implying morphological innovations were rhythmed by climatic changes and associated species turn-over that spread from the Eocene to Miocene, and were shaped principally by predation and shell buoyancy.

INTRODUCTION: Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. METHODS: Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. RESULTS: This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P

BACKGROUND: Motility is an important component of Salmonella enterica serovar Typhimurium (ST) pathogenesis allowing the bacteria to move into appropriate niches, across the mucus layer and invade the intestinal epithelium. In vitro, flagellum-associated motility is closely related to the invasive properties of ST. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is widely prescribed for the prophylaxis and treatment of diarrheal diseases caused by bacteria or antibiotics. In case of Salmonella infection, S.b-B has been shown to decrease ST invasion of T84 colon cell line. The present study was designed to investigate the impact of S.b-B on ST motility. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed on human colonic T84 cells infected by the Salmonella strain 1344 alone or in the presence of S.b-B. The motility of Salmonella was recorded by time-lapse video microscopy. Next, a manual tracking was performed to analyze bacteria dynamics (MTrackJ plugin, NIH image J software). This revealed that the speed of bacterial movement was modified in the presence of S.b-B. The median curvilinear velocity (CLV) of Salmonella incubated alone with T84 decreased from 43.3 µm/sec to 31.2 µm/sec in the presence of S.b-B. Measurement of track linearity (TL) showed similar trends: S.b-B decreased by 15% the number of bacteria with linear tract (LT) and increased by 22% the number of bacteria with rotator tract (RT). Correlation between ST motility and invasion was further established by studying a non-motile flagella-deficient ST strain. Indeed this strain that moved with a CLV of 0.5 µm/sec, presented a majority of RT and a significant decrease in invasion properties. Importantly, we show that S.b-B modified the motility of the pathogenic strain SL1344 and significantly decreased invasion of T84 cells by this strain. CONCLUSIONS: This study reveals that S.b-B modifies Salmonella's motility and trajectory which may account for the modification of Salmonella's invasion.

BACKGROUND: Sap sucking hemipteran aphids damage diverse crop species. Although delivery of ds-RNA or siRNA through microinjection/feeding has been demonstrated, the efficacy of host-mediated delivery of aphid-specific dsRNA in developing aphid resistance has been far from being elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Transgenic Arabidopsis expressing ds-RNA of Myzus persicae serine protease (MySP) was developed that triggered the generation of corresponding siRNAs amenable for delivery to the feeding aphids. M. persicae when fed on the transgenic plants for different time intervals under controlled growth conditions resulted in a significant attenuation of the expression of MySP and a commensurate decline in gut protease activity. Although the survivability of these aphids was not affected, there was a noticeable decline in their fecundity resulting in a significant reduction in parthenogenetic population. CONCLUSIONS/SIGNIFICANCE: The study highlighted the feasibility of developing host based RNAi-mediated resistance against hemipteran pest aphids.

The unified neutral theory of biodiversity and biogeography is increasingly accepted as an informative null model of community composition and dynamics. It has successfully produced macro-ecological patterns such as species-area relationships and species abundance distributions. However, the models employed make many unrealistic auxiliary assumptions. For example, the popular spatially implicit version assumes a local plot exchanging migrants with a large panmictic regional source pool. This simple structure allows rigorous testing of its fit to data. In contrast, spatially explicit models assume that offspring disperse only limited distances from their parents, but one cannot as yet test the significance of their fit to data. Here we compare the spatially explicit and the spatially implicit model, fitting the most-used implicit model (with two levels, local and regional) to data simulated by the most-used spatially explicit model (where offspring are distributed about their parent on a grid according to either a radially symmetric Gaussian or a 'fat-tailed' distribution). Based on these fits, we express spatially implicit parameters in terms of spatially explicit parameters. This suggests how we may obtain estimates of spatially explicit parameters from spatially implicit ones. The relationship between these parameters, however, makes no intuitive sense. Furthermore, the spatially implicit model usually fits observed species-abundance distributions better than those calculated from the spatially explicit model's simulated data. Current spatially explicit neutral models therefore have limited descriptive power. However, our results suggest that a fatter tail of the dispersal kernel seems to improve the fit, suggesting that dispersal kernels with even fatter tails should be studied in future. We conclude that more advanced spatially explicit models and tools to analyze them need to be developed.

BACKGROUND: Salmonella pathogenesis engages host cells in two-way biochemical interactions: phagocytosis of bacteria by recruitment of cellular small GTP-binding proteins induced by the bacteria, and by triggering a pro-inflammatory response through activation of MAPKs and nuclear translocation of NF-kappaB. Worldwide interest in the use of functional foods containing probiotic bacteria for health promotion and disease prevention has increased significantly. Saccharomyces boulardii is a non-pathogenic yeast used as a probiotic in infectious diarrhea. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we reported that S. boulardii (Sb) protected mice from Salmonella enterica serovar Typhimurium (ST)-induced death and prevented bacterial translocation to the liver. At a molecular level, using T84 human colorectal cancer cells, we demonstrate that incubation with Sb before infection totally abolished Salmonella invasion. This correlates with a decrease of activation of Rac1. Sb preserved T84 barrier function and decreased ST-induced IL-8 synthesis. This anti-inflammatory effect was correlated with an inhibitory effect of Sb on ST-induced activation of the MAPKs ERK1/2, p38 and JNK as well as on activation of NF-kappaB. Electron and confocal microscopy experiments showed an adhesion of bacteria to yeast cells, which could represent one of the mechanisms by which Sb exerts its protective effects. CONCLUSIONS: Sb shows modulating effects on permeability, inflammation, and signal transduction pathway in T84 cells infected by ST and an in vivo protective effect against ST infection. The present results also demonstrate that Sb modifies invasive properties of Salmonella.